The present invention relates to antibacterial agents of the carbapenem class, in which the 2-position sidechain is characterized by a biphenyl moiety, substituted by specific cationic and neutral substituents, as described in more detail further below.
Thienamycin was an early carbapenem antibacteiral agent having a broad spectrum; it has the following formula: ##STR2## Later, N-formimidoyl thienamycin was discovered; it has the formula: ##STR3##
More recently, U.S. Pat. No. 5,025,006 disclosed 2-biphenyl carbapenems of the formula: ##STR4## where R.sup.a is broadly classified as a neutral organic substituent. These compounds were found to be effective antibiotics.
Also, U.S. Pat. No. 5,011,832 disclosed 2-biphenyl carbapenems of the immediately above Formula where one of the R.sup.a substituents contains a quaternizeable nitrogen. These compounds were also found to be effective antibiotics.
As a class, the 2-biphenyl-carbapenems are not only of interest for a broad antibacterial spectrum such as that of thienamycin or N-formimidoyl thienamycin. Rather, their spectrum of activity of special interest is to gram positive microorganisms, especially methicillin resistant Staphyloccus aureus (MRSA). methicillin resistant Staphyloccus epidermidis (MRSE), and methicillin resistant coagulase negative Staphylococci (MRCNS). The 2-biphenyl carbapenems thus comprise an important contribution to therapy of these difficult to control pathogens. Within the class of 2-biphenyl carbapenems, there have been new found compounds having an unexpected level of safety. These compounds, to a surprising degree, have low seizure potential.